Recaída en el sistema nervioso central en leucemia mieloblástica aguda Sesión monográfica Recaída en el sistema nervioso central en leucemia mieloblástica aguda David Martínez Cuadrón 5 de mayo de 2011
Introducción Existe poca información acerca de la incidencia y factores de riesgo para recaída en el sistema nervioso central (SNC) en adultos con leucemia mieloblástica aguda (LMA) Recomendaciones de profilaxis en SNC establecidas a partir de estudios realizados en los años 80 y 90
Objetivos Valorar la incidencia acumulada y factores de riesgo de afectación del SNC en primera recaída en pacientes adultos con LMA y tratados con quimioterapia intensiva Resultados del tratamiento
Métodos Pacientes > 13 años Diagnosticados de LMA entre 1979 y 2009 en nuestro servicio Remisión completa (RC) tras quimioterapia intensiva sistémica 4 grupos de tratamiento Punción lumbar (PL) según grupos 51 características de paciente y enfermedad Lumbar puncture to examine cerebrospinal fluid (CSF) was not performed at the time of AML diagnosis except in patients with clinical suspicion of CNS infiltration (e.g., neurological signs and symptoms). Lumbar puncture was also performed to administer CNS relapse prophylaxis with intrathecal (IT) chemotherapy (methotrexate plus hydrocortisone alternating with cytarabine) in some patients treated with protocols used to treat groups 1 and 3. In those protocols, IT chemotherapy was indicated only in patients with FAB-M4 or M5 and a white blood cell (WBC) count >20109/L.
Métodos Diagnóstico de recaída: Tratamiento de recaída: PL si sospecha clínica Aspirado de médula ósea Tratamiento de recaída: Quimioterapia intratecal Radioterapia cráneo-espinal Quimioterapia sistémica When CNS relapse occurred, treatment comprised weekly IT chemotherapy with methotrexate plus hydrocortisone alternating with cytarabine until complete clearance of blasts in the CSF, followed by less frequent IT treatments as consolidation. Some patients received further craniospinal irradiation or concomitant systemic chemotherapy at the physician’s discretion.
Resultados RC en 458 pacientes (53%) Edad (años) : 54 (rango, 14-79) Sexo: 268 (59%) hombres Leucocitos (109/L ): 10 (rango, 0.5-375) FAB M4/M5: 148 (32%) LMA secundaria: 74 (16%) Infiltración del SNC al diagnóstico: 4 (1%) Profilaxis del SNC: 22 (5%) TPH: autólogo 106 (24%), alogénico 60 (13%) 458/859
Quimioterpia sistémica Resultados Sexo/edad (años) FAB Leucocitos (109/L) Tiempo hasta recaída en SNC (meses) Recaída medular Quimioterapia intratecal Quimioterpia sistémica Supervivencia desde recaída F/38 M4 68 15,7 Sí MTX IT (2) AraC IT (1) RTc 5-AZA + VP-16 0,5 F/31 M1 6 13,5 No MTX IT (4) AraC IT (3) POMP 13 M/42 M2 78 6,6 MTX IT (5) 4,5 M/64 16 2,9 AraC IT (4) 4 F/69 M5 43 10,1 AraC IT (2) MTZ + AraC 2 M/31 2.6 1,1 MTX IT (3) CBDCA 11,5 The median time to CNS relapse was seven months (range, 1–16 months) compared with nine months (range, 1–167 months) for isolated BM relapse. Three patients with isolated CNS relapse achieved complete clearance of blasts in the CSF and relief of symptoms. They all experienced a second relapse in the BM and died shortly after. Two of the three patients with simultaneous CNS and BM involvement died of infection during salvage chemotherapy with 5-azacytidine and etoposide or mitoxantrone and cytarabine. The third patient achieved a second CR with carboplatin and IT chemotherapy but experienced a second relapse in the CNS 257 days later and died. Overall, the median survival from CNS relapse was four months (range, 0.5–13 months).
Incidencia de recaída Frecuencia relativa de recaída en SNC: 2,5% (6/239) Incidencia acumulada a los 5 años: SNC: 1,3% MO: 51% IA por grupos: Protocolos antiguos: 3,9% Protocolos modernos: 0,3%
Incidencia Acumulada de Recaída en SNC (%) Análisis univariante Incidencia Acumulada de Recaída en SNC (%) Valor de P Leucocitos >40 x109/L 2.7 vs 0.9 0.15 LDH > 1x LSN 2.4 vs 0 0.04 FAB M4-M5 2 vs 1 0.36 Lisozima >30 5.2 vs 0 0.02 Protocolos antiguos 3.9 vs 0.3 0.002 No TPH 2.1 vs 0 0.06
Análisis multivariante Hazard Ratio Valor de P Protocolos modernos 00.07 0.02 Multivariate analysis identified modern protocols (groups 3 and 4) as the sole independent prognostic factor for CNS relapse (P=0.02, hazard ratio, 0.07 [95% confidence interval, 0.01–0.62])
Supervivencia tras recaída 2 pacientes fallecieron durante el tratamiento de inducción, en primera recaída 4 pacientes fallecieron tras la segunda recaída Mediana de supervivencia: 4 meses (rango, 0,5-13) Three patients with isolated CNS relapse achieved complete clearance of blasts in the CSF and relief of symptoms. They all experienced a second relapse in the BM and died shortly after. Two of the three patients with simultaneous CNS and BM involvement died of infection during salvage chemotherapy with 5-azacytidine and etoposide or mitoxantrone and cytarabine. The third patient achieved a second CR with carboplatin and IT chemotherapy but experienced a second relapse in the CNS 257 days later and died
Recaída en SNC: tratamiento
Conclusiones La afectación del SNC en primera recaída en adultos con LMA tratados con protocolos modernos, sin profilaxis del SNC, es muy baja Ninguna característica, clínica o biológica, se relaciona con mayor riesgo de recaída en SNC La terapia post-remisión puede haber disminuido su incidencia (TPH) By contrast, the CI of CNS relapse in patients treated with old chemotherapy approaches, which often included IT prophylaxis, was relatively high
Conclusiones Nuestros resultados no sugieren el uso de profilaxis en adultos con LMA By contrast, the CI of CNS relapse in patients treated with old chemotherapy approaches, which often included IT prophylaxis, was relatively high